1-77044499-A-G

Position:

• chr1-77044499-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_030965.3(ST6GALNAC5):​c.557A>G​(p.Tyr186Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ST6GALNAC5 NM_030965.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.33

Genes affected

ST6GALNAC5 (HGNC:19342): (ST6 N-acetylgalactosaminide alpha-2,6-sialyltransferase 5) The protein encoded by this gene is a Golgi type II transmembrane glycosyltransferase. The encoded protein catalyzes the transfer of sialic acid to cell surface proteins to modulate cell-cell interactions. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]

ST6GALNAC5 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.874

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ST6GALNAC5	NM_030965.3	c.557A>G	p.Tyr186Cys	missense_variant	3/5	ENST00000477717.6	NP_112227.1
ST6GALNAC5	NM_001320273.2	c.262-5759A>G		intron_variant			NP_001307202.1
ST6GALNAC5	NM_001320274.2	c.262-18476A>G		intron_variant			NP_001307203.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ST6GALNAC5	ENST00000477717.6	c.557A>G	p.Tyr186Cys	missense_variant	3/5	1	NM_030965.3	ENSP00000417583.1
ST6GALNAC5	ENST00000318803.6	n.557A>G		non_coding_transcript_exon_variant	3/5	5		ENSP00000436263.1
ST6GALNAC5	ENST00000488940.1	n.360A>G		non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1460964 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726706

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 06, 2023

The c.557A>G (p.Y186C) alteration is located in exon 3 (coding exon 3) of the ST6GALNAC5 gene. This alteration results from a A to G substitution at nucleotide position 557, causing the tyrosine (Y) at amino acid position 186 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.042	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Benign	-0.57	T
MutationAssessor	Pathogenic	3.3	M
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-7.8	D
REVEL	Pathogenic	0.71
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.98
MutPred		0.58		Loss of sheet (P = 0.0126);
MVP		0.35
MPC		1.2
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.81
gMVP		0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-77510184;